Dodion P, Chang B K, Egorin M J, Olman E A, Engisch K L, Bachur N R
Drug Metab Dispos. 1984 May-Jun;12(3):365-70.
We have investigated the metabolism and disposition, in mice, of 7-con-O-methylnogarol ( menogarol ; 7-OMEN), a new anthracycline antibiotic entering clinical trials. 7-OMEN, dissolved in 0.01 M glucuronic acid, was administered iv to mice (10 mg/kg). At specified times after injection, groups of mice were killed and 7-OMEN and metabolites were assayed in plasma and organs by HPLC. Plasma concentrations of 7-OMEN declined in triexponential fashion. The terminal t1/2 was 10.6 hr; the AUC was 10.13 microM X hr; the apparent Vc was 0.4 liter/m2, and the systemic clearance was 91.2 ml/min/m2. One metabolite, with the same HPLC characteristics as N- demethylmenogarol , was seen in plasma during the first 30 min after injection. 7-OMEN was distributed extensively to all tissues except brain. Initially, pulmonary concentrations of 7-OMEN were 15 times higher than those in any other organ and 30 times higher than those in plasma. Concentrations of 7-OMEN were the most persistent in spleen, kidney, and pancreas, and the least persistent in heart and liver. The AUC for 7-OMEN in organs was the greatest in lungs (605 nmol/g X hr), spleen (522 nmol/g X hr), and pancreas (430 nmol/g X hr), and least in heart (33 nmol/g X hr) and liver (60 nmol/g X hr). Kidneys and skeletal muscles had intermediate AUC values. In liver, two metabolites, one of which had the HPLC characteristics of N- demethylmenogarol , were seen. In other organs, the same metabolites were seen later and in small quantities.
我们研究了新型蒽环类抗生素7-顺式-O-甲基诺加罗（美诺加罗；7-OMEN）在小鼠体内的代谢和处置情况，该药物已进入临床试验阶段。将溶于0.01 M葡萄糖醛酸的7-OMEN静脉注射给小鼠（10 mg/kg）。注射后在特定时间点，处死小鼠组，通过高效液相色谱法（HPLC）测定血浆和器官中的7-OMEN及其代谢产物。7-OMEN的血浆浓度呈三指数方式下降。终末半衰期为10.6小时；曲线下面积（AUC）为10.13 μM·小时；表观分布容积（Vc）为0.4升/平方米，全身清除率为91.2毫升/分钟/平方米。注射后最初30分钟内在血浆中观察到一种代谢产物，其HPLC特征与N-去甲基美诺加罗相同。7-OMEN广泛分布于除脑以外的所有组织。最初，7-OMEN在肺中的浓度比其他任何器官高15倍，比血浆中高30倍。7-OMEN在脾脏、肾脏和胰腺中的浓度持续时间最长，在心脏和肝脏中持续时间最短。7-OMEN在各器官中的AUC在肺中最大（605 nmol/g·小时）、脾脏（522 nmol/g·小时）和胰腺（430 nmol/g·小时），在心脏中最小（33 nmol/g·小时），在肝脏中为（60 nmol/g·小时）。肾脏和骨骼肌的AUC值居中。在肝脏中观察到两种代谢产物，其中一种具有N-去甲基美诺加罗的HPLC特征。在其他器官中，相同的代谢产物出现较晚且数量较少。
